The objective of this research plan is to rigorously identify cancer- related genes and determine their full length coding sequences. Genes that are differentially expressed in normal versus tumor cells will be found by DNA array hybridization. These arrays will contain approximately 40,000 clones from the UniGene collection, representing the majority of currently known human genes. Sequence database searching will supplement this candidate list with genes that are closely related by sequence similarity to known proto-oncogenes and tumor suppressor genes, as well as genes generally thought to be important in mutation, tumor progression and metastasis. A panel of molecular biologists and cancer researchers from the Huntsman Cancer Institute at the University of Utah will review the selection criteria and candidate cDNAs. An automated DNA sequencing environment will assist the processing the plasmid cDNA clone, phage cDNA clones, and PCR fragments into finished sequence assemblies of full-length coding sequences. Expression profiles of the candidate cDNAs will be determined by array hybridization analysis using mRNA from the major tissues as probes. Size and complexity of the mRNA transcripts will be determined by Northern blot analysis. An automated instrument for high sensitivity, automated Northern analysis will be engineered, tested and implemented. Informatics tools for data management and visualization will be developed, and an Internet resource for analyzing cancer-related genes will be established. This combined effort will be conducted by an interdisciplinary group of biologists, engineers and computer programmers at the Utah Genome Center and the Huntsman Cancer Institute MicroArray Facility. The sequencing goals are 800 full IMAGE clone contigs and 250 full-length sequences completed per year. This new sequence will facilitate the efforts of researchers studying the molecular and cellular biology of cancer.